Chemically programmable immunity

ABSTRACT

The present invention is related to methods and compositions that are capable of immediately immunizing a human or animal against any molecule or compound. The present invention comprises an immunity linker molecule with at least two sites; (1) a first binding site that binds to an immune system molecule in a human or animal that has been preimmunized against the first binding site, and (2) one or more second binding sites that bind specifically to a desired compound or molecule. The first binding site and the second binding site(s) are linked by a linker portion of the molecule.

FIELD OF THE INVENTION

[0001] The present invention relates to methods and compositions forproviding immediate immunity to any desired antigen. The presentinvention also provides methods and compositions for treating a widevariety of diseases without having to wait for an immune response to bemounted by the human or animal being exposed to the disease.

BACKGROUND OF THE INVENTION

[0002] The term “antigen” is defined as anything that can serve as atarget for an immune response. The immune response can be eithercellular or humoral. The term “vaccine” is defined herein as asuspension or solution of antigenic moieties, usually consisting ofinfectious agents, or some part of the infectious agents, that isinjected into the body to produce active immunity. The antigenic moietymaking up the vaccine can be either a microorganism or a natural productpurified from a microorganism, a synthetic product or a geneticallyengineered protein, peptide, polysaccharide or similar product. The term“cell mediated immunity” is defined as an immune response mediated bycells rather than by antibody. It includes, but is not limited to,delayed type hypersensitivity and cytotoxic T cells. The term “adjuvant”as used herein is any or otherwise modifies the immune response. A“hapten” is defined herein as a substance that reacts selectively withappropriate antibodies or T cells, but the hapten itself is usually notimmunogenic. Most haptens are small molecules or small parts of largemolecules, but some macromolecules can also function as haptens. Theterm “conjugation” is defined herein as the covalent or other form oflinking two or more molecules. It can be accomplished either by chemicalmeans or in vivo by biologic means such as genetic engineering.

[0003] The process of immunization has been used for over a hundredyears to protect humans and animals against disease. The processgenerally comprises injecting an antigen that is related to the pathogenin the human or animal and waiting an appropriate amount of time,allowing the human or animal in which the pathogen was injected to mountan immune response. The time required for mounting an immune responsenormally is between approximately two weeks and several months for mostantigens. In most cases, a booster administration of the antigen isrequired to maintain the immune response. This booster is normally givenweeks or months after the initial administration of the antigen. Thus,immunization is of little use for immediate treatment of a disease.

[0004] A separate immunization procedure must be made for each pathogen,although in some cases several antigens are included in a singlevaccine. Every immunization carries with it a certain amount of riskthat must be considered before any immunization is recommended on awide-scale basis.

[0005] What is needed is a method of immunizing a human or animal thatcan result in an immediate immune response. In addition, a method ofimmunizing a human or animal by a single immunization would greatlyreduce the inherent risks in the vaccination procedure.

SUMMARY OF THE INVENTION

[0006] The present intention provides methods and compositions for theimmediate and specific immunization of a human or animal against apathogen or other undesired substance. The present invention, in oneembodiment, is designated an “immunity linker molecule” and comprises amolecule with multiple sites; a first binding site on the compound thatis antigenic and is capable of mounting an immune response in a human oranimal. After immunization of the human or animal, first binding sitewill then bind specifically to an antibody or other immune molecule thatwas induced by the immunization process. The molecule has a secondbinding site or sites that are capable of binding to one or moredesignated compounds. The present invention also includes a compoundthat contains only the first binding site or immunogenic site that ispresent in the immunity linker molecule. This compound that containsonly the first binding site or antigenic site is designated herein as“the immunizing molecule”.

[0007] According to the present invention, the immunity linker moleculecan be made in several ways. The immunizing molecule with the firstbinding site can be physically linked or conjugated to the molecule withthe second binding sites to the pathogen or other undesired substance.In another embodiment, the immunity linker molecule can be produced ormanufactured as a single molecule containing the first binding site orimmunizing site and the second binding sites. The immunity linkermolecule can be any type of compound including protein, nucleic acid ora combination thereof. The first binding sight can be a hapten that isconjugated to a larger molecule.

[0008] In practicing the present invention, the human or animal is firstimmunized conventionally against the immunizing molecule. This processincludes administering the molecule to the human or animal and thenwaiting an appropriate amount of time for an necessary, the immunizingmolecule can be administered with an adjuvant and/or a booster may begiven to the animal at appropriate times. These methods of immunizing ahuman or animal are well known to one of ordinary skill in the art. Thehuman or animal that has been immunized against the immunizing moleculenow has antibodies that will bind the immunizing molecule when it ispresent in the blood or other fluid.

[0009] When the preimmunized human or animal is challenged with apathogen or toxic substance, an immunity linker molecule that contains abinding site to the pathogen or toxic substance is administered to thehuman or animal. The immunity linker molecule binds at one site to theantibody that was previously induced, and binds to the pathogen at thesecond site thereby providing an immune complex of the antibody bound tothe immunity linker molecule which is now bound to the pathogen. Thebody now recognizes the immune complexes and processes them in a normalmanner.

[0010] Accordingly, it is an object of the present invention to providea method and composition for the immediate and specific immunization ofa human or animal.

[0011] It is yet another object of the present invention to provide amethod and composition for immediately immunizing an immunologicallynaive human or animal.

[0012] It is another object of the present invention to provide a methodand composition that enables one to quickly and easily select a desiredantigen and immediately immunize the human or animal against thatantigen.

[0013] Another object of the present invention is to provide a methodand composition that will only require a single immunization to protectagainst a wide variety of pathogens and toxic substances, therebyreducing the risks of multiple vaccinations.

[0014] Yet another object of the present invention is to provide amethod and composition that will allow health care professionals toimmediately immunize a patient against a wide variety of pathogensand/or toxins.

[0015] These and other objects, features and advantages of the presentinvention will become apparent after a review of the following detaileddescription of the disclosed embodiment.

BRIEF DESCRIPTION OF DRAWINGS

[0016]FIG. 1 illustrates the structure of the immunity linker molecule.

[0017]FIG. 2 illustrates the immunity linker molecule bound at one siteto an antibody and, at a second site, to a desired molecule, therebyforming an immune complex.

DETAILED DESCRIPTION OF THE INVENTION

[0018] The present invention is related to methods and compositions thatare capable of immediately immunizing a human or animal against anymolecule or compound. The present invention comprises an immunity linkermolecule with at least two sites; (1) a first binding site that binds toan immune system molecule in a human or animal that has beenpreimmunized against the first binding site, and (2) one or more secondbinding sites that bind specifically to a desired compound or molecule.The first binding site and the second binding site(s) are linked by alinker portion of the molecule.

[0019] The present invention comprises methods and compositions for theimmediate and specific immunization of a human or animal against apathogen or other undesired substance. According to the presentinvention, a human or animal can be immediately immunized against achosen antigen simply by administering to the human or animal theimmunity linker molecule with the appropriate second binding site.According to the present invention, one can provide immediate immunityto any chosen antigen on the basis of the pre-existing immunity to theimmunizing molecule by administration of a synthetic chemical

[0020] In practicing the present invention, the human or animal is firstimmunized conventionally against the immunizing molecule. This processincludes appropriately administering the molecule to the human or animaland then waiting an appropriate amount of time for an immune response tobe mounted in the human or animal. The preferred method of administeringthe immunizing molecule is by injection. If necessary, the immunizingmolecule can be administered with an adjuvant and/or a booster may begiven to the animal at appropriate times. These methods of theimmunizing a human or animal are well known to one of ordinary skill inthe art. The human or animal that has been immunized against theimmunizing molecule now has antibodies that will bind the immunizingmolecule when it is present in the blood or other bodily fluid.

[0021] The immunizing molecule optionally can be administered withagents such as adjuvants, preservatives, diluents, emulsifiers,stabilizers, and other known components that are known and used inimmunization procedures in the prior art. Any adjuvant system known inthe art can be used in the composition of the present invention. Suchadjuvants include, but are not limited to, Freund's incomplete adjuvant,Freund's complete adjuvant, polydispersed β-(1,4) linked acetylatedmannan (“Acemannan”), Titermax® (polyoxyethylene-polyoxypropylenecopolymer adjuvants from CytRx Corporation), modified lipid adjuvantsfrom Chiron Corporation, saponin derivative adjuvants from CambridgeBiotech, killed Bordetella pertussis, the lipopolysaccharide (LPS) ofgram-negative bacteria, large polymeric anions such as dextran sulfate,and inorganic gels such as alum, aluminum hydroxide, or aluminumphosphate. A preferred adjuvant system is Freund's incomplete adjuvant.Another preferred adjuvant system is Freund's complete adjuvant. Themethod of immunization and the adjuvants used are not critical to theinvention. Thus, any method known in the art can be used, and anyadjuvant system known in the art can be used.

[0022] According to the present invention, immediate immunity to, forexample, a pathogen, can be established in a human or animal that isimmunologically naive to the pathogen by administering to the human oranimal that has been immunized against the immunizing molecule theimmunity linker molecule that contains a binding site to the pathogen.The immunity linker molecule binds at one site to the antibody that waspreviously induced, and binds to the pathogen at the second site,thereby providing an immune complex of the antibody bound to theimmunity linker molecule which is now bound to the pathogen. The bodynow recognizes the immune complexes and processes the complexes in anormal manner.

[0023] According to the present invention, the immunity linker moleculecan be made in several ways. The immunizing molecule can be physicallylinked or conjugated to the molecule with the binding sites to thedesired substance. In another embodiment, the immunity linker moleculecan be produced or manufactured as a single molecule containing themultiple sites. In yet another embodiment, the immunity linker moleculeconsists of two active ends connected together by a rigid or flexiblespacer such as a double helical region of RNA. The purpose of the spaceris to hold the two ends of the linker together, while preventing themfrom interacting.

[0024] The immunity linker molecule can be a protein, peptide, ornucleic acid molecule or any combination thereof, including, but notlimited to, RNA molecules, DNA molecules or derivatives thereof.Preferably, the immunity linker molecule is comprised of RNA moleculesand are produced according to the SELEX process. This process isdescribed completely in the list of references attached hereto and areincluded herein by reference in their entirety.

[0025] The immunity linker molecule is shown schematically in FIG. 1.The immunity linker molecule 10 comprises a first binding site 15 whichis antigenic, a linking portion of the molecule 20 and a second bindingsite 35 that is capable of binding a specific molecule. The secondbinding site 35 site or sites are preferably aptamers that have beenproduced by the SELEX process. However, it is to be understood that thesecond binding site does not have to be an aptamer, but can be any typeof molecule that has the desired physical attributes, i.e., the secondbinding site being capable of binding to a specific molecule. It is tobe understood that the immunity linker molecule can have more than onebinding site to a single substance or can have multiple binding sitesagainst multiple substances. The linking portion of the molecule linksthe first binding site 15 and the second binding site 35. The linkingportion 15 of the molecule can be double stranded nucleic acid, butother linking molecules can be used in the present invention. FIG. 2schematically shows the immunity linker molecule with an antibody 40bound to the first binding site 15 of the molecule and a molecule 45bound to the second binding site 35 on the immunity linker molecule 10.

[0026] It is to be understood that the immunity linker molecule can beany type of molecule that is capable of being manipulated so that it iscapable of (1) mounting an immunity response, and (2) binding a desiredmolecule or molecules. The preferred type of compound is nucleic acidor, preferably, modified nucleic acid such as 2′-fluoro- or2′-amino-2′-deoxypyrimidine containing nucleic acids. Nucleic acidsusing these bases are much more stable than naturally occurring nucleicacids. (See Aptamers as tools in molecular biology and immunology, M.Famulok and G. Mayer, Cur.Top. Micro. Immunobiol., 1999, 243, 123-146.)

[0027] The immunity linker molecule can be administered to a patientintramuscularly, subcutaneously, orally, intravenously, or through themucosal membranes. The immunity linker molecule can be use in immunizinga human or animal against a wide variety of substances, including, butnot limited to, bacteria, fungi, viruses, toxic substances, and drugs.

[0028] The present invention is particularly useful in the militarywhere troops may be unexpectedly exposed to a pathogen, toxin, or to atoxic chemical substance. Military personnel are preimmunized againstthe immunizing molecule, i.e., that portion of the immunity linkermolecule that binds to the antibody. Then, if the military personnel areunexpectedly challenged with a pathogen, the appropriate immunity linkermolecule can be administered to the military personnel, therebyimmediately protecting them against the pathogen or other toxicsubstance. The present invention can be used to prevent and/or treatorganisms including, but not limited to, anthrax, dengue virus, orMarburg virus

[0029] Likewise, pharmacies can have a library of different immunitylinker molecules available for a variety of different pathogens andtoxic substances. If the patient has been preimmunized against theimmunizing portion of the linker, then he or she will be immediatelyimmunized against the pathogen or toxic substances.

[0030] It should be understood, of course, that the foregoing relatesonly to preferred embodiments of the present invention and that numerousmodifications or alterations may be made therein without departing fromthe spirit and the scope of the invention as set forth in thisdisclosure.

1. An immunity linker molecule, the immunity linker molecule containingat least one first site that binds to an immune system molecule and atlease one second site that binds to a desired compound or molecule. 2.The immunity linker molecule of claim 1 wherein the first site binds toan antibody.
 3. The antibody of claim 2 wherein the antibody is from ahuman or animal that has been preimmunized against the first site. 4.The immunity linker molecule of claim 1, wherein the desired compound ormolecule is a microorganism.
 5. The immunity linker molecule of claim 4wherein the microorganism is a bacteria, virus, or fungus.
 6. Theimmunity linker molecule of claim 1, wherein the compound or molecule isa drug.
 7. The immunity linker molecule of claim 1, wherein the immunitylinker molecule is an aptomer.
 8. A method of immunizing a human oranimal against a molecule or compound comprising administering to thehuman or animal an immunity linker molecule, the immunity linkermolecule containing at least one first site second site that binds to adesired compound or molecule.
 9. The method of claim 8, wherein thehuman or animal has been preimmunized against the first site on theimmunity linker molecule.
 10. The method of claim 8, wherein theimmunity the desired compound or molecule is a microorganism.
 11. Themethod of claim 10 wherein the microorganism is a bacteria, virus, orfungus.
 12. The method of claim 8, wherein the compound or molecule is adrug.
 13. The method of claim 1, wherein the immunity linker molecule isan aptomer.
 14. A method of preimmunizing a human or animal comprisingimmunizing a human or animal against a molecule that contains a firstsite that is immunogenic, the first site being present on an immunelinker molecule, the immune linker molecule also containing at lease onesecond site that binds to a desired compound or molecule.